Advances in quantitative image processing have facilitated greatly the capacity of structural magnetic resonance imaging (MRI) to detect subtle and previously unappreciated changes in brain regions among HIV+ persons without dementia. These provide a powerful tool to advance knowledge of key clinical and neuropathological features of neuroAIDS as they have evolved since the introduction of HAART. These new methods may allow for mapping more precisely subtle brain changes among HIV+ subjects with significant comorbid conditions such as substance dependence, which are currently not well understood. We propose to conduct a two-year methodological pilot to establish feasibility of morphometric studies MRI at UIC in collaboration with investigators at the University of Pittsburgh who have developed Automated Language Programming, a state of the art post processing system that has been employed successfully to study subtle changes in cerebral morphology. Over the next two years we will perform MRI scans on a total of 40 individuals recruited from an existing cohort of subjects from a larger study led by the PI, with varying history of HIV and substance dependence and establish the capability to define and compare subtle changes in selected brain regions of critical interest in the study of neuroAIDS and addiction, to be conducted with a small group of subjects enrolled in a larger study of HIV and substance dependence led by the PI. Results of this project have significant translational potential for characterizing and tracking CNS involvement among substance-dependent HIV+ persons without frank dementia. Findings will enable us to formulate and test new and exciting hypotheses regarding neuroAIDS and its real life consequences, including vulnerability to risky sexual behavior, in significantly understudied population with multiple health problems. PUBLIC HEALTH RELEVANCE People with HIV/AIDS are living longer since the introduction of potent antiretroviral therapies but HIV still affects the brain and can impair memory and other cognitive functions, so it is important to develop new methods for tracking these brain changes. This project will test a very precise brain imaging method that is able to pick up very small brain changes before development of serious neurologic problems such as dementia. The information gathered in this project may be able to help us develop treatments with the potential to prevent dementia or other mental problems